Prostatic carcinoma (PCA) is of considerable importance in the cancer statistics of Western countries. In the Federal Republic of Germany alone there are about 8000 fatalities each year. The incidence, approx. 10 % of all malignant diseases in men, makes PCA the second most frequent tumour in the male sex. For example, 96000 new cases and 26000 fatalities were recorded in the USA in 1987.
In spite of intensive efforts in research and clinical treatment, the age-adjusted mortality rate in the USA, for example, remained largely constant from 1950 to 1980, while in smaller European countries a marked increase has even been observed, which because of its higher incidence in older age groups must be seen in relation to a shift in the age structure of the population.
The androgen-dependence of prostatic carcinoma has been known in scientific literature since the investigations of Huggins and Hodges (cf. Cancer Res. 1, 293-297 (1941)).
Further to these studies, an endocrine treatment of the prostatic carcinoma was proposed in which it was shown that a regression of the tumour can be achieved by androgen-ablation (cf. Emmett et al., J.Urol. 83, 471-484 (1960)). In addition to the local displacement of the androgen from its cellular receptor by anti-androgens, such as flutamide or cyproterone acetate, the direct suppression of circulating androgens by surgical means, such as orchietomy, hypophysectomy or adrenalectomy, or by the administration of substances such as diethylstilbestrol or aminoglutethimide, has therefore become usual in the treatment of advanced prostatic carcinomas.
This endocrine treatment results in subjective success in 60 to 80% of cases. However, an objective improvement occurs in only 20 to 40% of patients. In addition, a considerable lengthening of the symptom-free interval may be achieved.
The androgen-ablative therapy does not, however, result in the patients being cured. The majority of patients die after an initial period of remission, usually following the almost obligatory conversion of the tumour from the initially hormone-dependent state into the hormone-independent state.
The aetiology of this conversion of the tumour into the androgen-independent state has not yet been finally clarified, although more recent investigations indicate an initial heterogeneity of the tumour. That is to say, both androgen-dependent and androgen-independent cells can be detected in the tumour. Even the recently disclosed therapy with gonadotropin-releasing hormone analogues (GnRH-analogues), such as leuprolide (cf. Schally et al., Int.J.Gynaecol.Obstet. 18, 318-324, (1980)) is based on a reduction of the peripheral androgen level by inhibition of the pituitary-gonad axis. The main advantage of this form of therapy compared with conventional treatment lies in its reduced side-effects, while it is not possible to prove objective superiority, for example, over therapy with diethylstilbestrol (cf. inter alia Tolis, G. et al., Proc. Nat. Acad. Scien. 79, 1658-1662 (1982)).
Finally, the "complete" androgen-ablation through the combination of GnRH-analogues with non-steroidal anti-androgens, as proposed by Labrie, has not as yet resulted in any clear improvement in the laboratory or in clinical studies (cf. Labrie et al., J.Steroid.Biochem. 23, 833-841 (1985)).
In summary, it can therefore be said that none of the newer therapy regimens have lead to a significant improvement in the remission and survival rate compared with classical endocrinological therapy.